Hyperadrenal Disorders

Question 1

Describe the effects of excess cortisol on protein and fat synthesis.

Answer 1

Decrease protein synthesis

Increase fat synthesis

Question 2

Explain why people with Cushing’s disease get stretch marks.

Answer 2

Put on a lot of fat quickly, which stretches the skin.

Because protein synthesis is switched off, can’t make the protein required for skin growth so the skin tears.

Question 3

List 10 clinical features of Cushing’s syndrome.

Answer 3

Moon face 
Interscapular fat pad (buffalo hump) 
Proximal myopathy 
Centripetal obesity
Easy bruising  
Striae 
Thin skin 
Osteoporosis 
Diabetes   
Hypertension + hypokalaemia

Question 4

Why does Cushing’s syndrome cause hypertension and hypokalaemia?

Answer 4

At high concentrations, cortisol can have mineralocorticoid effects –> increased Na+ absorption + K+ excretion

Question 5

State 4 causes of Cushing’s syndrome.

Answer 5

Excess steroid intake (glucocorticoids)
Pituitary dependent Cushing’s disease
Ectopic ACTH from lung cancer
Adrenal adenoma secreting cortisol

Question 6

What are the 3 main tests used to diagnose Cushing’s syndrome?

Answer 6

24-hour collection for urine free cortisol
Blood diurnal cortisol levels (or midnight serum cortisol)
Low dose dexamethasone suppression test

Question 7

Describe the results you’d expect from a normal subject and a patient with Cushing’s syndrome in the 24-hour urine free cortisol and blood diurnal cortisol tests.

Answer 7

Normal: lower cortisol at night + high cortisol in the morning.
Cushing’s: high cortisol all the time (problem- cortisol levels are affected by stress)

Question 8

Explain the scientific basis of the low dose dexamethasone suppression test. Describe what you would see in a normal result and a Cushing’s result.

Answer 8

Dexamethasone is an artificial steroid so by giving this extra glucocorticoid, it should suppress ACTH + reduce cortisol production.
Normal: Suppress ACTH. Blood test = 0 cortisol
Cushing’s: Cortisol will remain high despite presence of dexamethasone.

Question 9

State the surgical treatments for Cushing’s syndrome.

Answer 9

Dependent on cause:
Transsphenoidal Hypophysectomy (for Cushing’s disease)
Bilateral adrenalectomy
Unilateral adrenalectomy for adrenal mass

Question 10

State 2 drugs that are used to treat Cushing’s syndrome before surgery.

Answer 10

Metyrapone

Ketoconazole

Question 11

What is the problem with the low dose dexamethasone test?

Answer 11

It doesn’t tell you whether the issue is adrenal, pituitary or ectopic

Question 12

Which enzyme is inhibited by metyrapone?

Answer 12

11-Beta-hydroxylase

Question 13

What effect does metyrapone have on the steroid synthesis pathway?

Answer 13

Prevents conversion of:
11-deoxycorticosterone –> corticosterone
+
11-deoxycortisol –> cortisol
Thus, no corticosterone or cortisol is produced

Question 14

State 2 uses of metyrapone.

Answer 14

Prep. Cushing’s patient for surgery (improves healing abilities + makes them better surgical candidates)
Control of Cushing’s symptoms after radiotherapy (radiotherapy has a delayed effect)

Question 15

State 2 negative aspects of metyrapone.

Answer 15

1. Causes accumulation of 11-deoxycorticosterone (because it doesn’t have negative feedback effects on ACTH axis)
   11-deoxycorticosterone has mineralocorticoid effects so causes Na+ + water reabsorption, predisposing to HYPERTENSION.
2. Inhibits 2 limbs of the steroid synthesis pathway so funnels the precursors towards the sex steroid synthesis pathway.
   This leads to increased adrenal androgens, which causes hirsuitism in women

Question 16

What is ketoconazole and why is it no longer used?

Answer 16

An anti-fungal, which inhibits steroidogenesis.

No longer used because of its hepatotoxicity (except “off label” in prep for surgery)

Question 17

What are the effects of ketoconazole on steroid production?

Answer 17

Ketoconazole inhibits enzyme which converts cholesterol to pregnenolone
So, it inhibits the production of glucocorticoids, mineralocorticoids + sex steroids.

Question 18

State the main unwanted action of ketoconazole. How do we avoid this?

Answer 18

LIVER DAMAGE (possibly fatal) 
Monitor liver function weekly, clinically + biochemically

Question 19

What is Conn’s syndrome?

Answer 19

Aldosterone secreting adenoma of the adrenal gland (zona glomerulosa)

Question 20

What are the 2 main features of Conn’s syndrome?

Answer 20

Hypertension

Hypokalaemia

Question 21

What is primary hyperaldosteronism?

Answer 21

Hyperaldosteronism caused by an adrenal adenoma.

Question 22

What can you test to exclude secondary hyperaldosteronism?

Answer 22

Check for suppression of the renin-angiotensin system.

Conn’s: Aldosterone= high + Renin= suppressed (by high BP)

Question 23

What is the usual treatment plan for someone with Conn’s syndrome?

Answer 23

Medical management (spironolactone) 
Surgery to remove the tumour

Question 24

What is spironolactone and how does it work?

Answer 24

Spironolactone converted to Canrenone (a competitive mineralocorticoid receptor antagonist)
Blocks Na+ reabsorption + K+ excretion (K+ sparing diuretic)

Question 25

What treatment would you give for someone with bilateral adrenal hyperplasia?

Answer 25

Long-term spironolactone
Don’t want to remove both adrenals because then they wouldn’t produce any cortisol or aldosterone so give them long-term spironolactone to reduce the effects of excess aldosterone.

Question 26

Describe the pharmacokinetics of spironolactone.

Answer 26

Orally active

Highly protein-bound + metabolised in the liver

Question 27

State 2 unwanted effects of spironolactone.

Answer 27

Not very specific to mineralocorticoid receptor:
Progesterone receptor agonist: causes menstrual irregularities
Androgen receptor antagonist: causes gynaecomastia

Question 28

Name another mineralocorticoid receptor antagonist that has fewer side effects than spironolactone.

Answer 28

Eplerenone

Question 29

What is phaeochromocytoma?

Answer 29

Tumour of the adrenal medulla that is producing excessive amounts of catecholamines (A + NA)

Question 30

List 6 features of phaeochromocytoma

Answer 30

Episodic severe hypertension (in young)  
Anxiety
Headaches
Nausea
Sweating
Dizziness

Question 31

State some fatal consequences of phaeochromocytoma.

Answer 31

Hypertension: Myocardial infarction + stroke
High adrenaline: ventricular fibrillation + death
It is a MEDICAL EMERGENCY

Question 32

Describe the steps that must be taken when preparing a phaeochromocytoma patient for surgery.

Answer 32

Anaesthetic could precipitate a hypertensive crisis.
Give patient an alpha-blocker to prevent vasoconstriction caused by A binding to alpha-receptors.
Alpha-blockers cause a drop in BP so they are usually given with IV fluid.
Give beta-blockers to prevent tachycardia.
Once all the receptors are blocked, a massive release in A will not be able to have its effects.

Question 33

What percentage of phaeochromocytoma is intra-adrenal?

Answer 33

90%
It is a very rare condition
More common in certain inherited conditions